Many viruses activate a single RNA to enable successful infections

A gene is a DNA sequence that encodes the instructions for when and where to make a particular protein. But most of the DNA in our genome—well over ninety percent—is not composed of genes.

The argument over the role of this seemingly extraneous DNA has swung back and forth. In the 1970s, it was thought to be generally useless junk. But in 2012, the ENCODE consortium (the ENCyclopedia Of DNA Elements—cute, right?) posited that most of the DNA had some sort of activity. Earlier this year, a new analysis insisted again that it’s just junk.

Even as that debate was raging among researchers, viruses have used some of the noncoding DNA for their own purposes: to hijack our cellular metabolism and promote their own replication. Results are reported in Science.

ENCODE concluded that a lot of noncoding DNA may be functional because much of it is transcribed into RNA, even if that RNA isn’t translated into proteins. There’s evidence that some of these RNAs are functional, as they play a role in controlling other genes (though clearly not every RNA plays this role). Some of these RNAs, especially those that are relatively long (over two hundred bases) but still don’t get made into proteins, have been shown to be induced by viral infection.

New work done in China has determined that viruses actually take advantage of one of these RNA molecules. The long noncoding RNA in question is made by both mice and men. It is induced by a variety of viruses, and when it’s eliminated, these viruses cannot replicate. How all these different viruses activate the same gene isn’t clear at this point.

The RNA binds to and activates an enzyme (glutamic-oxaloacetic transaminase) involved in many important metabolic processes, including amino acid metabolism, long-chain fat use, and a basic respiratory cycle. By inducing the production of this long noncoding RNA, viruses shift the metabolic enzyme into hyperdrive in order to spur viral replication. That suggests that the enzyme itself might make a useful drug target.

We know a fair amount about the different tricks viruses use to enter cells and the means they use to get out. Less clear are the molecular mechanisms underlying how viruses subvert a cell’s metabolism toward their own nefarious ends. This work suggests that viruses, unlike biologists, are not especially interested in the evolutionary necessity and purpose of noncoding DNA. They just use it.